7NI4

Human ATM kinase domain with bound M4076 inhibitor

7NI4 の概要

• エントリーDOI: 10.2210/pdb7ni4/pdb
• EMDBエントリー: 12343 12345 12346 12347 12350
• 分子名称: Serine-protein kinase ATM, ZINC ION, 8-(1,3-dimethylpyrazol-4-yl)-1-(3-fluoranyl-5-methoxy-pyridin-4-yl)-7-methoxy-3-methyl-imidazo[4,5-c]quinolin-2-one (3 entities in total)
• 機能のキーワード: kinase, inhibitor, dna damage response, cancer research, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 703283.09

構造登録者

Stakyte, K.,Rotheneder, M. (登録日: 2021-02-11, 公開日: 2021-09-01, 最終更新日: 2025-07-02)

主引用文献

Stakyte, K.,Rotheneder, M.,Lammens, K.,Bartho, J.D.,Gradler, U.,Fuchss, T.,Pehl, U.,Alt, A.,van de Logt, E.,Hopfner, K.P.
Molecular basis of human ATM kinase inhibition.
Nat.Struct.Mol.Biol., 28:789-798, 2021

PubMed Abstract: Human checkpoint kinase ataxia telangiectasia-mutated (ATM) plays a key role in initiation of the DNA damage response following DNA double-strand breaks. ATM inhibition is a promising approach in cancer therapy, but, so far, detailed insights into the binding modes of known ATM inhibitors have been hampered due to the lack of high-resolution ATM structures. Using cryo-EM, we have determined the structure of human ATM to an overall resolution sufficient to build a near-complete atomic model and identify two hitherto unknown zinc-binding motifs. We determined the structure of the kinase domain bound to ATPγS and to the ATM inhibitors KU-55933 and M4076 at 2.8 Å, 2.8 Å and 3.0 Å resolution, respectively. The mode of action and selectivity of the ATM inhibitors can be explained by structural comparison and provide a framework for structure-based drug design.

PubMed: 34556870
DOI: 10.1038/s41594-021-00654-x

実験手法

ELECTRON MICROSCOPY (3 Å)